PXD058162-1

PXD058162 is an original dataset announced via ProteomeXchange.

Title	Insights into the FOXE3 Transcriptional Network from Exploration of the Impact of a Regulatory Variant in Complex Microphthalmia
Description	FOXE3 encodes a highly conserved transcription factor essential for lens development, which is critical for proper eye formation. Biallelic variants in FOXE3 are associated with ocular anomalies, particularly complex microphthalmia (CM), characterized by defects in both the anterior segment and lens. Using next-generation sequencing (NGS) and Sanger sequencing, we identified a heterozygous nonsense variant in compound heterozygosity with a novel single nucleotide variant (SNV) located in a conserved non-coding region 3 kb upstream of FOXE3 in a patient with CM. Genetically engineered mouse lines carrying either the non-coding variant (Foxe3rv) or a frameshift mutation (Foxe3-) in homozygosity (Foxe3rv/rv and Foxe3-/-), along with compound heterozygous (Foxe3rv/Foxe3-) animals, revealed significant differences in the prevalence of ocular anomalies between wild-type controls and mice with homozygous or compound heterozygous mutations, highlighting the detrimental impact of these genetic variants. Furthermore, the progressive decline in FOXE3 protein levels across genotypes underscores its essential role in normal lens development and overall eye structure. These findings illuminate the intricate relationship between genetic variants and their effects on protein functionality and phenotype. In addition, our analysis demonstrated that the non-coding variant impairs USF2 binding, while Usf2 knockdown underscored its essential role in downregulating Foxe3, positioning it as a promising candidate gene in ocular development. These insights emphasize the importance of identifying disease-causing non-coding variants to enhance diagnostic precision for ocular developmental defects and to enrich our understanding of the regulatory mechanisms that govern eye development genes. Finally, this work provides new elements to understand the general mechanisms of ocular growth which, when impaired, leads to microphthalmia.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_23:09:09.835.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ino Karemaker
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-22 00:38:05	ID requested
⏵ 1	2025-08-24 23:09:10	announced

10.1167/iovs.66.11.47;

Plaisanci, é J, Ang, é, e C, Erjavec E, Raymond-Letron I, Douet JY, Goetz M, Vincent-Delorme C, Karemaker ID, Baltissen M, Vermeulen M, Valdivia L, Jabot-Hanin F, David P, Hadjadj D, Monsef YA, Lyazrhi F, Calvas P, Rozet JM, Chassaing N, Fares-Taie L, Insights Into the FOXE3 Transcriptional Network and Disease Mechanisms From the Investigation of a Regulatory Variant Driving Complex Microphthalmia. Invest Ophthalmol Vis Sci, 66(11):47(2025) [pubmed]

submitter keyword: FOXE3, Microphthalmia

Lucas Fares-Taie
contact affiliation	Laboratoire de Génétique Ophtalmologique, INSERM U1163, Institut Imagine, Paris, France
contact email	lucas.fares-taie@inserm.fr
lab head
Ino Karemaker
contact affiliation	ETH Zürich
contact email	ino.karemaker@bc.biol.ethz.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/08/PXD058162

PRIDE project URI

• PRIDE
  1. PXD058162
     1. Label: PRIDE project
     2. Name: Insights into the FOXE3 Transcriptional Network from Exploration of the Impact of a Regulatory Variant in Complex Microphthalmia